STEROID HORMONES, HIV-INFECTED CELLS AND HIV GENES

类固醇激素、HIV 感染细胞和 HIV 基因

• 批准号: 3241641
• 负责人: E B THOMPSON
• 金额: $ 15.11万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-02-01 至 1994-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3241641
• 关键词: AIDS; CD4 molecule; HIV infections; Herpesviridae disease; cell bank /registry; clone cells; cytolysis; estrogens; gene expression; glucocorticoids; hormone receptor; human immunodeficiency virus; human tissue; messenger RNA; molecular pathology; mouse mammary tumor virus; nuclear magnetic resonance spectroscopy; peptide hormone biosynthesis; progestins; ribosomal RNA; steroid hormone; transfection; transposon /insertion element; virus cytopathogenic effect; virus genetics

This project is designed to do two things: first, to test the hypothesis that changes in steroid hormone effects are involved in the direct and indirect cytopathicity of HIV; and second, to use a DNA response element for glucocorticoids as a cis-active control over HIV genes to determine their functions quantitatively. Steroid hormones have profound effects on lymphoid cells directly and also indirectly, through influences on many peptide hormones and their receptors. We will investigate the effects of steroids on peripheral blood lymphoid cells of HIV infected individuals and on several infected cell lines. This will require studies of cellular effects of steroids, analysis of steroid receptors, and examination of the interactive effects of steroids with several peptide hormones and their receptors. Limited reports raise the possibility that HIV is glucocorticoid-inducible. We will thoroughly test this possibility. The exact function of several HIV genes is unknown, as are the quantitative relationships between specific gene products and overall HIV replication and cytopathicity. We will place the glucocorticoid response element from the MMTV LTR in a cis relationship to HIV or specific HIV genes, to provide glucocorticoid-regulatable HIV genes for study in transfected cells. Our clonal lines of CEM cells with known lesions in the glucocorticoid response system, should be of particular value in these studies.

该项目旨在做两件事：第一，测试 假设类固醇激素作用的变化与 HIV的直接和间接细胞病变性；其次，使用 糖皮质激素的 DNA 反应元件作为顺式活性对照 对 HIV 基因进行定量分析以确定其功能。 类固醇激素直接对淋巴细胞产生深远影响 也间接地通过影响许多肽激素 及其受体。 我们将研究类固醇的影响 HIV感染者外周血淋巴细胞的影响 在几种受感染的细胞系上。 这将需要研究 类固醇的细胞效应，类固醇受体的分析，以及 检查类固醇与几种药物的相互作用 肽激素及其受体。 有限的报告提出了 HIV 可能是糖皮质激素诱导的。 我们将 彻底测试这种可能性。 一些 HIV 基因的确切功能尚不清楚，正如 特定基因产物之间的数量关系 总体 HIV 复制和细胞病变。 我们将把 顺式 MMTV LTR 中的糖皮质激素反应元件 与 HIV 或特定 HIV 基因的关系，以提供 糖皮质激素调节的 HIV 基因用于转染研究 细胞。 我们的 CEM 细胞克隆系具有已知病变 糖皮质激素反应系统，在以下方面应具有特别价值： 这些研究。